Migraine Disorders, Heart Disease, Cerebrovascular Accident, TIA (Transient Ischemic Attack), Vascular Diseases, Peripheral Vascular Diseases
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of telcagepant in the treatment of acute migraine in participants with stable vascular disease. Acetaminophen/paracetamol (APAP) will be used as an active comparator in this study. The primary hypothesis of this study is that telcagepant 300 mg is superior to placebo.
Interventions
DRUGTelcagepant
Telcagepant (MK-0974) (300 mg soft gel capsules or 280 mg tablets)
Acetaminophen/Paracetamol (500 mg X 2 dosage units)
Placebo 300 mg soft gel capsules or placebo 280 mg tablet.
DRUGPlacebo to Acetaminophen/Paracetamol
Placebo to acetaminophen/paracetamol (500 mg X 2 dosage units)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable coronary artery disease for 3 months or more * 18 years of age or older with a history of migraine with or without aura * Must use acceptable contraception throughout the study
Exclusion criteria
* Pregnant, breast-feeding, or planning to become pregnant during this study * 50 years of age or older when migraines began * Other pain syndromes that might interfere with study assessments, uncontrolled psychiatric conditions, dementia, or significant neurological disorders (other than migraine) * History of gastric, or small intestinal surgery, or has a disease that causes malabsorption
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Freedom at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 2 hours post-dose (Up to 6 weeks) | Pain Freedom (PF) at 2 hours post-dose (Period 1, Attack 1) defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at baseline to no pain (Grade 0). Headache severity was subjectively rated by the participant at predefined time points on a scale of Grade 0 to Grade 3: Grade 0 - No pain; Grade 1 - Mild pain; Grade 2 - Moderate Pain; and Grade 3 - Severe Pain. |
| Number of Participants Who Experienced an Adverse Event (AE) Within 14 Days Post-dose | Within 14 days of any dose of study medication (Up to 16 weeks) | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
| Number of Participants Discontinuing Study Drug Due to an AE Within 48 Hours Post-dose | Up to 48 hours post-dose (Up to 14 weeks) | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Absence of Photophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 2 Hours post-dose (Up to 6 weeks) | The participant recorded whether photophobia (sensitivity to light) was present or absent at each of the predefined time points. |
| Percentage of Participants With Pain Relief at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 2 hours post-dose (Up to 6 weeks) | Pain Relief (PR) at 2 hours post-dose (first migraine attack), with pain relief defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 at 2 hours post-dose. Headache severity was subjectively rated by the participant at predefined time points on a scale of Grade 0 to Grade 3: Grade 0 - No pain; Grade 1 - Mild pain; Grade 2 - Moderate Pain; and Grade 3 - Severe Pain. |
| Percentage of Participants With Sustained Pain Freedom (SPF) at 2 to 24 Hours Post-dose | Up to 24 hours post-dose (Up to 14 weeks) | SPF from 2 to 24 hours post-dose is defined as PF at 2 hours, with no administration of either rescue medication or the optional second dose and with no occurrence thereafter of a mild/moderate/severe headache during the 2 to 24 hours after dosing with the study medication. |
| Percentage of Participants With Absence of Nausea at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 2 hours post-dose (Up to 6 weeks) | The participant recorded whether nausea was present or absent at each of the predefined time points. |
| Number of Participants With a Confirmed Vascular Event Within 48 Hours Post-dose | Up to 48 hours after the dose of any study medication (Up to 14 weeks) | Confirmed Vascular Event included cardiac events, cerebrovascular events, and peripheral vascular events. |
| Percentage of Participants With Absence of Phonophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 2 hours post-dose (Up to 6 weeks) | The participant recorded whether phonophobia (sensitivity to sound) was present or absent at each of the predefined time points. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telcagepant 300 mg→APAP 1000 mg Participants receive up to 12 doses of telcagepant (280 mg tablet/capsule 300 mg), orally, and placebo to acetaminophen/paracetamol (APAP) (2- 500 mg dry filled capsules), orally, for up to 12 migraine attacks in Period 1 (6 weeks). Participants receive APAP and placebo to telcagepant for up to 12 doses, for up to 12 migraine attacks in Period 2 (6 weeks). | 56 |
| Placebo and APAP 1000 mg→Telcagepant 300 mg Participants receive 1 dose of placebo to APAP and placebo to telcagepant for the first migraine attack and then up to 11 doses of APAP and placebo to telcagepant for up to 11 migraine attacks in Period 1 (6 weeks). Participants receive up to 12 doses of telcagepant and placebo to APAP for up to 12 migraine attacks in Period 2 (6 weeks). | 58 |
| Total | 114 |
Baseline characteristics
| Characteristic | Telcagepant 300 mg→APAP 1000 mg | Placebo and APAP 1000 mg→Telcagepant 300 mg | Total |
|---|---|---|---|
| Age, Continuous | 56.6 Years STANDARD_DEVIATION 10.1 | 55.7 Years STANDARD_DEVIATION 10 | 56.1 Years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 33 Participants | 36 Participants | 69 Participants |
| Sex: Female, Male Male | 23 Participants | 22 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 98 | 0 / 86 |
| serious Total, serious adverse events | 1 / 98 | 0 / 86 |
Outcome results
Primary
Number of Participants Discontinuing Study Drug Due to an AE Within 48 Hours Post-dose
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to 48 hours post-dose (Up to 14 weeks)
Population: The APaT Population consisted of all participants who received at least 1 dose of study medication were included in the treatment group according to the medication actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Number of Participants Discontinuing Study Drug Due to an AE Within 48 Hours Post-dose | 0 Participants |
| Placebo | Number of Participants Discontinuing Study Drug Due to an AE Within 48 Hours Post-dose | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE) Within 14 Days Post-dose
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Within 14 days of any dose of study medication (Up to 16 weeks)
Population: All-Patients-as-Treated (APaT) population consisted of all participants who received at least 1 dose of study medication were included in the treatment group according to the medication actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Number of Participants Who Experienced an Adverse Event (AE) Within 14 Days Post-dose | 21 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) Within 14 Days Post-dose | 14 Participants |
Primary
Percentage of Participants With Pain Freedom at 2 Hours Post-dose (Period 1, Migraine Attack 1)
Pain Freedom (PF) at 2 hours post-dose (Period 1, Attack 1) defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at baseline to no pain (Grade 0). Headache severity was subjectively rated by the participant at predefined time points on a scale of Grade 0 to Grade 3: Grade 0 - No pain; Grade 1 - Mild pain; Grade 2 - Moderate Pain; and Grade 3 - Severe Pain.
Time frame: 2 hours post-dose (Up to 6 weeks)
Population: The full-analysis set (FAS) included participants treated for a migraine attack. Participants had both a baseline value and at least 1 post-dose efficacy measurement for pain severity prior to, or including, the 2-hour time point. Participants were excluded from this analysis who did not have a baseline pain score or post-dose data through 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Percentage of Participants With Pain Freedom at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 25.0 Percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 18.9 Percentage of participants |
p-value: 0.32995% CI: [0.62, 4.25]Regression, Logistic
Secondary
Number of Participants With a Confirmed Vascular Event Within 48 Hours Post-dose
Confirmed Vascular Event included cardiac events, cerebrovascular events, and peripheral vascular events.
Time frame: Up to 48 hours after the dose of any study medication (Up to 14 weeks)
Population: The APaT Population consisted of all participants who received at least 1 dose of study medication were included in the treatment group according to the medication actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Number of Participants With a Confirmed Vascular Event Within 48 Hours Post-dose | 0 Participants |
| Placebo | Number of Participants With a Confirmed Vascular Event Within 48 Hours Post-dose | 0 Participants |
Secondary
Percentage of Participants With Absence of Nausea at 2 Hours Post-dose (Period 1, Migraine Attack 1)
The participant recorded whether nausea was present or absent at each of the predefined time points.
Time frame: 2 hours post-dose (Up to 6 weeks)
Population: The FAS population included participants treated that migraine attack, and had both a baseline value and at least 1 post-dose efficacy measurement for nausea prior to, or including, the 2-hour time point. Participants were excluded from this analysis who did not have a baseline nausea score or post-dose data through 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Percentage of Participants With Absence of Nausea at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 80.8 Percentage of Participants |
| Placebo | Percentage of Participants With Absence of Nausea at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 69.8 Percentage of Participants |
p-value: 0.20195% CI: [0.73, 4.6]Regression, Logistic
Secondary
Percentage of Participants With Absence of Phonophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1)
The participant recorded whether phonophobia (sensitivity to sound) was present or absent at each of the predefined time points.
Time frame: 2 hours post-dose (Up to 6 weeks)
Population: The FAS population included participants treated that migraine attack, and had both a baseline value and at least 1 post-dose efficacy measurement for phonophobia prior to, or including, the 2-hour time point. Participants were excluded from this analysis who did not have a baseline phonophobia score or post-dose data through 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Percentage of Participants With Absence of Phonophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 65.4 Percentage of participants |
| Placebo | Percentage of Participants With Absence of Phonophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 58.5 Percentage of participants |
p-value: 0.64895% CI: [0.52, 2.85]Regression, Logistic
Secondary
Percentage of Participants With Absence of Photophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1)
The participant recorded whether photophobia (sensitivity to light) was present or absent at each of the predefined time points.
Time frame: 2 Hours post-dose (Up to 6 weeks)
Population: The FAS population included participants treated that migraine attack, and had both a baseline value and at least 1 post-dose efficacy measurement for photophobia prior to, or including, the 2-hour time point. Participants were excluded from this analysis who did not have a baseline photophobia score or post-dose data through 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Percentage of Participants With Absence of Photophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 53.8 Percentage of Participants |
| Placebo | Percentage of Participants With Absence of Photophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 58.5 Percentage of Participants |
p-value: 0.64795% CI: [0.31, 2.07]Regression, Logistic
Secondary
Percentage of Participants With Pain Relief at 2 Hours Post-dose (Period 1, Migraine Attack 1)
Pain Relief (PR) at 2 hours post-dose (first migraine attack), with pain relief defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 at 2 hours post-dose. Headache severity was subjectively rated by the participant at predefined time points on a scale of Grade 0 to Grade 3: Grade 0 - No pain; Grade 1 - Mild pain; Grade 2 - Moderate Pain; and Grade 3 - Severe Pain.
Time frame: 2 hours post-dose (Up to 6 weeks)
Population: The FAS Population included participants treated that migraine attack, and had both a baseline value and at least 1 post-dose efficacy measurement for pain severity prior to, or including, the 2-hour time point. Participants were excluded from this analysis who did not have a baseline pain score or post-dose data through 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 63.5 Percentage of Participants |
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Post-dose (Period 1, Migraine Attack 1) | 56.6 Percentage of Participants |
p-value: 0.4295% CI: [0.59, 3.5]Regression, Logistic
Secondary
Percentage of Participants With Sustained Pain Freedom (SPF) at 2 to 24 Hours Post-dose
SPF from 2 to 24 hours post-dose is defined as PF at 2 hours, with no administration of either rescue medication or the optional second dose and with no occurrence thereafter of a mild/moderate/severe headache during the 2 to 24 hours after dosing with the study medication.
Time frame: Up to 24 hours post-dose (Up to 14 weeks)
Population: The FAS population was participants treated that migraine attack, and had both a baseline value and at least 1 post-dose efficacy measurement for pain severity prior to, or including, the 2-hr. time point. Participants were excluded from this analysis for not having a baseline pain score, post-dose data through 24 hrs, or a recurrence question.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 300 mg | Percentage of Participants With Sustained Pain Freedom (SPF) at 2 to 24 Hours Post-dose | 19.2 Percentage of Participants |
| Placebo | Percentage of Participants With Sustained Pain Freedom (SPF) at 2 to 24 Hours Post-dose | 15.4 Percentage of Participants |
p-value: 0.57995% CI: [0.47, 3.85]Regression, Logistic